Synthesis and characterization of self-assembled polymer-camptothecin conjugates for precision oncology
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Date
2025-03-06
Authors
Γιαννόπουλος, Παναγιώτης
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Abstract
In recent years, the need of anticancer medication is deemed necessary, due to the growth of worldwide number of cancer cases. Polymer Drug Conjugates (PDCs) are one of the most recent and innovative ways of battling cancer and initiating an effective cancer treatment. In this thesis, polymer drug conjugates, utilizing camptothecin, a potent topoisomerase I inhibitor, which prevents cancer DNA replication, are created, with the goal of improving the delivery and enhancing the efficacy of camptothecin, due to its poor water solubility, instability in biological environments and toxic side effects.
There are two primary approaches to synthesize PDCs, post-polymerization modification and the polymerizable monomers, with the latter being studied in this thesis, using N-(2-hydroxypropyl)methacrylamide (HPMA) as a starting molecule. Then, two paths are being followed regarding the linker of the PDC, one that is focused on the breakage of a disulfide bond, merging HPMA with DTDP (3,3'-dithiodipropionic acid) and one without, merging HPMA with Succinic Anhydride. Generally, linkers respond differently to external stimuli, such as pH or temperature, but in this thesis, ultrasound is being used, with a main focus of dropping the drug-payload (CPT) from outside the patient’s body.
To identify the products of synthesis and RAFT polymerization, certain characterization methods are being utilized, namely, Nuclear Magnetic Resonance (NMR) spectroscopy, Critical Aggregation Concentration (CAC) and Dynamic Light Scattering (DLS) to measure the respective nanoparticle size. These techniques provided insights regarding the structural integrity, molecular weight, size and stability of the polymer-drug conjugates, proving the successful conjugation of CPT and the effective formation of nanoparticles with the desired properties for drug delivery.
The drug release experiments demonstrated the pH-sensitive drug release profiles. During acidic conditions (pH 4.9) a larger quantity of CPT was observed in correlation to physiological pH values (pH 7.4). In one important instance the addition of phthalocyanine (Pc), proved that there is higher drug release in acidic environments and along with the use of ultrasound, more CPT can be released from the nanoparticles.
In conclusion, polymer-CPT conjugates represent a promising strategy for overcoming the limitations of conventional CPT delivery. By utilizing innovative polymer designs and stimuli-responsive mechanisms, these conjugates offer enhanced drug delivery, reduced toxicity, and improved therapeutic efficacy.
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Keywords
Polymer-drug conjugates, Camptothecin, Drug delivery system